SECTION 22 ACUTE VENOUS THROMBOEMBOLIC DISEASE

CHAPTER 145 
Acute Deep Venous Thrombosis:
Epidemiology and Natural History
ANDREA T. OBI, JORDAN KNEPPER, and THOMAS W. WAKEFIELD

EPIDEMIOLOGY 1918 Geography and Ethnicity  1924

Incidence 1918 Inflammatory Bowel Disease  1924
Populations Affected  1919 Systemic Lupus Erythematosus  1924
Risk Factors  1919 Varicose Veins  1925
Age 1919 Iliac Vein Compression  1925
Immobilization 1921 Popliteal Vein Entrapment  1925
Travel 1921 Other Risk Factors  1925
History of Venous Thromboembolism  1921 NATURAL HISTORY  1926
Malignancy 1922 Recanalization 1926
Surgery 1922 Recurrent Venous Thrombosis  1926
Trauma 1923 Mortality 1926
Pregnancy 1923
Oral Contraceptives and Hormonal Therapy  1923
Blood Group  1924

Acute venous thromboembolism (VTE), including deep

venous thrombosis (DVT) and pulmonary embolism (PE),
are the most common preventable cause of hospital death1
and a source of substantial long-term morbidity.2-4 The
impact on health is so great that the Surgeon General of the
United States issued a “Call to Action” to combat VTE.5 An
understanding of the risk factors and natural history of VTE
is essential in guiding prophylaxis, diagnosis, and treatment.
In addition, recognizing underlying risk factors and the
multifactorial nature of VTE may aid in the identification
of situations likely to provoke thrombosis in both high-risk
individuals and those with unexplained thromboembolism.
Furthermore, understanding the natural history of VTE is
important in defining the relative risks and benefits of antico-
agulation, as well as the duration of treatment in individual
patients.
1918
EPIDEMIOLOGY
Incidence
The incidence of recurrent, fatal, and nonfatal VTEs is esti-
mated to exceed 900,000 cases annually in the United States
alone.6 A 35-year population-based study using the Rochester
Epidemiology Project database of Olmsted County Minnesota
demonstrated an overall average age- and sex-adjusted annual
VTE incidence of 122 per 100,000 person-years (DVT, 56 per
100,000; PE, 66 per 100,000).7 This study also demonstrated
higher age-adjusted rates among men than women (134 vs. 115
per 100,000, respectively). First-time VTEs are approximated
to occur in 250,000 US white individuals annually.8 When
compared with other racial populations, whites have a lower
incidence of VTE than do African Americans (104 vs. 141 per

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 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History 1918.e1

Abstract Keywords
The incidence of recurrent, fatal and nonfatal venous throm- venous thromboembolism
boembolism (VTE) is estimated to exceed 900,000 cases annually. recurrent thrombosis
VTE is associated with a number of risk factors. These include DVT
age, immobilization, travel, history of VTE, malignancy, surgery, PE
trauma, pregnancy, oral contraceptives and hormonal therapy, risk factors
blood group, geography and ethnicity, inflammatory bowel
disease, systemic lupus erythematosus, varicose veins, iliac vein
compression, popliteal vein entrapment, among others. The
main complications of VTE include recurrent thrombosis
and mortality, especially related to pulmonary embolism,
along with post-thrombotic morbidity related to deep venous
thrombosis.

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 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History 1919

100,000) and a higher incidence of VTE than do Hispanics and

Asian/Pacific Islanders combined (104 vs. 21 per 100,000).9 TABLE 145.1  Risk Factors for Acute Deep Venous
However, the problem of VTE is not just isolated to the United Thrombosis and Pulmonary Embolism
States; it is a global issue. The estimates of VTE across the Odds 95% Confidence
European Union were 684,019 cases of DVT, 434,723 cases Risk Factor for DVT or PE Ratio Interval
of PE, with 543,454 VTE-related fatalities.10
Hospitalization
With recent surgery 21.72 9.44-49.93
Populations Affected Without recent surgery 7.98 4.49-14.18
The incidence of VTE varies with the population studied, use Trauma 12.69 4.06-39.66
of thromboprophylaxis, the intensity of screening, and the Malignant Neoplasm
accuracy of the diagnostic test employed. For example, individuals
With chemotherapy 6.53 2.11-20.23
with acute spinal cord injury who were screened systematically
with venography demonstrated DVT at a rate of 81%.11 However, Without chemotherapy 4.05 1.93-8.52
medical-surgical intensive care unit (ICU) patients who received Prior central venous catheter or 5.55 1.57-19.58
thromboprophylaxis had a DVT rate reported at 10% to 18%,12 pacemaker
compared with those who were not given DVT prophylaxis Prior superficial vein thrombosis 4.32 1.76-10.61
having a rate of 25% to 32%.12,13 Interestingly, the risk of VTE Neurologic disease with 3.04 1.25-7.38
in the critically ill is not limited to the time actually spent in extremity paresis
the ICU. A single-center study showed that of the VTEs Varicose Veins
diagnosed in the critically ill, 64% were diagnosed with a VTE Age 45 years 4.19 1.56-11.30
after discharge from the ICU. It is suggested that prolonged
Age 60 years 1.93 1.03-3.61
immobility after discharge from the ICU may have contributed
to the high rate of DVT.14 Similarly, prolonged immobility Age 75 years 0.88 0.55-1.43
contributes to increased rates of VTE in nursing home residents.15 Congestive Heart Failure
In summary, it appears that medical-surgical ICU patients are Thromboembolism not 9.64 2.44-38.10
at lower risk for DVT compared with acute spinal cord injury, categorized as a cause of death
trauma, or neurosurgery patients, but at a comparable risk to at postmortem
patients who have had major orthopedic surgery, and at higher Thromboembolism categorized as 1.36 0.69-2.68
risk than medical-surgical ward patients.13,16 Furthermore, a a cause of death at postmortem
more recent study noted a high (15.2%) rate of DVT in critically DVT, Deep venous thrombosis; PE, pulmonary embolism.
ill trauma patients within the first week that did not vary Modified from Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep
regardless of whether or not prophylaxis was used.17 vein thrombosis and pulmonary embolism: a population-based case-control
study. Arch Intern Med. 2000;160:809.

Risk Factors
DVT occurring in the setting of a recognized risk factor is often
defined as a secondary event, whereas those that occur in the
absence of risk factors is termed primary or idiopathic.18 Known
risk factors for DVT are listed in Table 145.1.
The high incidence of acute DVT in hospitalized patients,
the availability of objective diagnostic tests, and the existence
of clinical trials evaluating prophylactic measures have helped
to more readily identify high-risk groups in this population
compared with the outpatient population. Malignancy, surgery,
and trauma within the previous 3 months remain significant
risk factors for outpatient thrombosis, whereas the prevalence of
surgery and malignancy is higher among inpatients with DVT.19,20
Approximately 47% of outpatients with a documented DVT
have one or more recognized risk factors.19 The incidence of
VTE proportionally increases with the number of risk factors.21
The 2005 Caprini score is currently the most used system in
the country (Fig. 145.1).12,22
Age
VTE occurs in all ages, although a higher incidence has con-
sistently been associated with advanced age. In a community-
based study of phlebographically documented DVT, the yearly
incidence of DVT was noted to increase progressively from
almost 0 in childhood to 7.65 cases per 1000 in men and 8.22
cases per 1000 in women older than 80 years.23 The incidence
of DVT increased 30-fold from those age 30 years to those
older than 80 years. Rosendaal24 similarly noted an incidence
of 0.006 per 1000 children younger than 14 years, which rose
to 0.7 per 1000 among adults 40 to 54 years old. Furthermore,
Hansson and colleagues25 found the prevalence of objectively
documented thromboembolic events among men increased from
0.5% at age 50 years to 3.8% at age 80 years.
The influence of age on the incidence of VTE is likely mul-
tifactorial. The number of thrombotic risk factors increases with
age, with three or more risk factors being present in only 3% of
hospitalized patients younger than 40 years but in 30% of those
40 years and older.21 Interestingly, it also appears that the number
of risk factors required to precipitate thrombosis decreases with
age.24 This may be related to an acquired prothrombotic state
associated with aging because higher levels of thrombin activation
markers are found among older people.26 Advanced age also
has been associated with anatomic changes in the soleal veins

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1920 SECTION 22 Acute Venous Thromboembolic Disease

Patient’s name:________________ Age: ___ Sex: ___ Wgt: ___ lbs

Choose all that apply
Each risk factor represents 1 point Each risk factor represents 2 points
• Age 41–60 years • Age 60–74 years
• Minor surgery planned • Major surgery (>60 minutes)
• History of prior major surgery • Arthroscopic surgery (>60 minutes)
• Varicose veins • Laparoscopic surgery (>60 minutes)
• History of inflammatory bowel disease • Previous malignancy
• Swollen legs (current) • Central venous access
• Obesity (BMI >30) • Morbid obesity (BMI >40)
• Acute myocardial infarction (<1 month) Each risk factor represents 5 points
• Congestive heart failure (<1 month) • Elective major lower extremity arthroplasty
• Sepsis (<1 month) • Hip, pelvis or leg fracture (<1 month)
• Serious lung disease incl. pneumonia (<1 month) • Stroke (<1 month)
• Abnormal pulmonary function (COPD) • Multiple trauma (<1 month)
• Medical patient currently at bed rest • Acute spinal cord injury (paralysis) (<1 month)
• Leg plaster cast or brace • Major surgery lasting over 3 hours
• Other risk factors_____________________
For women only (each represents 1 point)
Each risk factor represents 3 points • Oral contraceptives or hormone replacement therapy
• Age over 75 years • Pregnancy or postpartum (<1 month)
• Major surgery lasting 2–3 hours • History of unexplained stillborn infant, recurrent spontaneous
• BMI >50 (venous stasis syndrome) abortion (≥3), premature birth with toxemia or
• History of SVT, DVT/PE growth-restricted infant
• Family history of DVT/PE
• Present cancer or chemotherapy
• Positive factor V leiden
• Positive prothrombin 20210A
• Elevated serum homocysteine
• Positive lupus anticoagulant
• Elevated anticardiolipin antibodies
• Heparin-induced thrombocytopenia (HIT)
• Other thrombophilia
Type_________________________________

Total risk factor score

Please see following page for prophylaxis safety considerations
revised May 16, 2006

Prophylaxis regimen
Total risk factor score Incidence of DVT Risk level Prophylaxis regimen Legend
0–1 <10% Low risk No specific measures; early ambulation ES — Elastic stockings
IPC — Intermittent
2 10–20% Moderate risk ES or IPC or LDUH, or LWMH
pneumatic compression
3–4 20–40% High risk IPC or LDUH, or LMWH alone or in LDUH — Low dose
combination with ES or IPC unfractionated heparin
LMWH — Low molecular
5 or more 40–80% Highest risk Pharmacological: LDUH, LMWH*, Warfarin*,
weight heparin
1–5% mortality or Fac Xa* alone or in combination with
Fac Xa — Factor X inhibitor
ES or IPC

Prophylaxis safety considerations: Check box if answer is ‘YES’

Anticoagulants: Factors associated with increased bleeding
Is patient experiencing any active bleeding?
Does patient have (or has had history of) heparin-induced thrombocytopenia?
Is patient’s platelet count <100,000/mm3?
Is patient taking oral anticoagulants, platelet inhibitors (e.g., NSAIDS, clopidigrel, salicylates)?
Is patient’s creatinine clearance abnormal? If yes, please indicate value –––––––––––––––
If any of the above boxes are checked, the patient may not be a candidate for anticoagulant therapy and you should consider alternative
prophylactic measures.
Intermittent pneumatic compression (IPC)
Does patient have severe peripheral arterial disease?
Does patient have congestive heart failure?
Does patient have an acute superficial/deep vein thrombosis?
If any of the above boxes are checked, then patient may not be a candidate for intermittent compression therapy and you should consider
alternative prophylactic measures.

Figure 145.1  The Caprini risk factor tool to predict the risk of venous thromboembolism. DVT, Deep venous
thrombosis; PE, pulmonary embolism. (From Wakefield T, Henke P. Complications in Surgery. 2nd ed. Philadelphia:
Lippincott Williams & Wilkins; 2011:353.)

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 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History
and more pronounced stasis in the venous valve pockets.27,28
We have also noted biologic changes with aging in our research
laboratory, such as elevations in P-selectin, tissue factor (TF),
antiphospholipid antibodies, and procoagulant microparticles,
supporting the effect of age on venous thrombogenesis.
Venous diseases, including VTE, are usually regarded as rare
in young children,3 with an incidence of 0.006 per 1000 children
younger than 14 years,24 whereas the incidence in hospitalized
children younger than 18 years has been estimated to be 0.05%.29
Early mobilization and discharge may partially explain the lower
incidence in children.29 However, the diagnosis is often not
considered in pediatric patients, and few studies have systemati-
cally evaluated children for DVT. Over time the number of
recognized cases in hospitalized children has increased from
0.3 to 28.8 per 10,000 from 1992 to 2005.30
VTE in children is almost always associated with recognized
thrombotic risk factors,24,31-33 and multiple risk factors are often
required to precipitate thrombosis.24 DVT may occur in as
many as 3.7% of pediatric patients immobilized in halo-femoral
traction for preoperative treatment of scoliosis,34 4% of children
hospitalized in the ICU,35 and 10% of children with spinal cord
injuries.36,37 Symptomatic postoperative DVT is regarded as
unusual in children, although there are few data from studies
using routine surveillance,38 and autopsy-identified PE is
approximately four times more frequent in pediatric patients
who have undergone surgery than in the general pediatric medical
population.31 Other thrombotic risk factors in hospitalized chil-
dren are local infection and trauma, immobilization,33 inherited
hypercoagulable states,24 oral contraceptive use,39 lower limb
paresis,34 and the use of femoral venous catheters.40 Outpatient
DVT is often associated with a prior DVT and thrombophilia.30
Immobilization
Immobilization is a risk factor for VTE. Stasis in the soleal
veins and behind the valve cusps is worsened by inactivity of
the calf muscle pump,28 which is associated with an increased
risk of DVT. The prevalence of lower extremity DVT in autopsy
studies also parallels the duration of bed rest, with an increase
during the first 3 days of confinement and a rapid rise to very
high levels after 2 weeks. DVT was found in 15% of patients
dying after 0 to 7 days of bed rest, in comparison with 79%
to 94% of those dying after 2 to 12 weeks.27 Preoperative
immobilization is also associated with a twofold increase in risk
of postoperative DVT,41 and DVT among stroke patients is
significantly more common in paralyzed or paretic extremities
(53% of limbs) than in nonparalyzed limbs (7%).42 Patients
with neurologic disease and extremity paresis or plegia have a
threefold higher risk for DVT and PE, which appears to be
independent of hospital confinement.43
Travel
Immobilization as a thrombotic risk factor extends to include
prolonged travel, particularly the “economy class syndrome,”
which occurs in people who have sat in a cramped position
during extended aircraft flights.44 Several case series have reported
the occurrence of PE in relation to extended travel,44-49 although
none has rigorously examined the prevalence relative to that of
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1921
the general population, and few have thoroughly reported the
presence of other risk factors. A high prevalence of preexisting
venous disease and other thrombotic risk factors in this group
of patients has sometimes been noted.26,49 The question of
prolonged travel as a risk factor is moderated by observations
that extreme duration of venous stasis alone may fail to produce
thrombosis50 and that no consistent rheologic or prothrombotic
changes have been demonstrated during prolonged travel.26,51
However, PE is the second leading cause of travel-related death,
accounting for 18% of 61 deaths, suggesting that a relationship
cannot be excluded.48
More evidence that a connection between travel and DVT
and PE has accumulated. In a case-control study, Ferrari and
associates found52 that long distance travel increased the risk
of DVT, with an odds ratio (OR) of 4.0, and Samama53 made
similar observations (OR, 2.3). Scurr and colleagues54 found a
10% risk of calf DVT in patients who traveled without compres-
sion stockings. Lapostolle and coworkers55 observed that over
an 86-month period, 56 of 135.3 million airline passengers
had severe PE. The frequency among those who traveled more
than 5000 km was 150 times as high as those who traveled less
than 5000 km. In another case-control study, Paganin and
associates56 observed a high incidence of VTE in patients with
risk factors for DVT who traveled long distances: in particular,
history of previous VTE (OR, 63.3), recent trauma (OR, 13.6),
presence of varicose veins (OR, 10), obesity (OR, 9.6), immobil-
ity during flight (OR, 9.3), and cardiac disease (OR, 8.9)
increased the risk of DVT. These investigators concluded that
low mobility during flight was a modifiable risk factor for
development of PE and that travelers with risk factors should
increase their mobility.57
After a consensus meeting, the World Health Organization
published the following conclusions: an association probably
exists between air travel and DVT; such an association is likely
to be small and mainly affects passengers with additional risk
factors for VTE; similar links may exist for other forms of
travel.58 The available evidence does not permit an estimation
of actual risk.
History of Venous Thromboembolism
Approximately 23% to 26% of patients presenting with acute
DVT have a previous history of thrombosis,23,59 and histologic
studies confirm that acute thrombi are often associated with
fibrous remnants of previous thrombi in the same or nearby
veins.60 Depending on sex and age, population-based studies
have demonstrated that recurrent VTE occurs in 2% to 9%
of people.3
The risk of recurrent VTE is higher among patients with
idiopathic DVT.61 In addition, primary hypercoagulability
appears to have a significant role in many recurrences. Simioni
and associates61 reported the cumulative incidence of recurrent
thrombosis among patients who are heterozygous for the factor
V Leiden mutation to be 40% at 8 years of follow-up, 2.4-fold
higher than in patients without the mutation, although the
importance of heterozygous factor V Leiden to recurrent
thrombosis has been questioned.62 den Heijer and colleagues63
estimated that 17% of recurrent thromboembolic events may
1922 SECTION 22 Acute Venous Thromboembolic Disease
be due to hyperhomocysteinemia. A similar relationship between
impaired fibrinolysis and recurrent DVT has been suggested
by several investigators, although the methodologic validity of
these findings has been questioned.64
Malignancy
Approximately 20% of all first-time VTE events are associated
with malignancy.65 An estimated 1 in 200 individuals with
malignancy will develop either DVT or PE, a fourfold higher
risk than those without malignancy.43 Considering all-cause
mortality of in-hospital death for cancer patients, one in seven
will die of PE.66 Strikingly, the discovery of an occult malignancy
associated with an otherwise first-time idiopathic VTE is as
high as 12% to 17% in some series.67,68 In another 5% to 11%
of patients, malignancy appears within 1 to 2 years of presenta-
tion for DVT.67-69 Several series have documented a significantly
higher risk of malignancy in patients with presumed idiopathic
DVT.67,70 Among such patients, 7.6% have been noted to have
a malignancy during follow-up, with an OR of 2.3 in comparison
with those with secondary thrombosis.68 The incidence of occult
malignancy diagnosed within 6 to 12 months of an idiopathic
DVT is 2.2 to 5.3 times higher than that expected from general
population estimates.71,72 The highest rates of VTE are associated
with pancreatic malignancies, followed by kidney, ovary, lung,
and stomach.73
The underlying mechanisms contributing to the hyperco-
agulable state in malignancy have been well studied and are
multifactorial. Venous compression secondary to tumor growth,
cancer-associated thrombocytosis, immobility, indwelling central
lines, and chemotherapy or radiation therapy are all risk factors
that increase the possibility of VTE.74 However, the systemic
prothrombotic response seen in malignancy is mediated by
cytokines, inhibitors of fibrinolysis, and procoagulants.75
Tumor cells can directly initiate hemostasis through con-
stitutive expression of TF. TF is not normally expressed on
resting vascular endothelium but rather induced by chemical
mediators during times of inflammation or vessel damage to
bind factors VII and VIIa. This complex of TF and factor VII
activates factors X and XI through proteolysis, leading to the
generation of thrombin.76 Another mediator in malignancy-
associated VTE is cancer procoagulant (CP). The role of CP
in coagulation is limited to its association with malignancy
because it has not been identified in normal healthy tissue.
CP serves as a direct activator of factor X, independent of
the presence of factor VIIa. The platelet adhesion molecules
glycoprotein Ib and glycoprotein IIb/IIIa (GPIIb/IIIa) have also
been identified on tumor cells, allowing for platelet activation and
aggregation.77
The prothrombotic contribution of cytokines such as vascular
endothelial growth factor (VEGF), tumor necrosis factor-α
(TNF-α), and interleukin-1 (IL-1) mediate their actions through
induction of TF on vascular endothelium, monocytes, and
leukocytes.76,78 In addition, IL-1 and TNF-α downregulate the
expression of thrombomodulin, the receptor for thrombin, on
the endothelial surface. This results in a decrease in thrombin-
thrombomodulin complexes, the activating complex of protein
C, a natural anticoagulant.76,78 Furthermore, IL-1 and TNF-α
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stimulate the production of plasminogen activator inhibitor 1
(PAI-1), the main physiologic inhibitor of fibrinolysis.79
As many as 90% of patients with cancer have abnormal
coagulation parameters, including increased levels of coagulation
factors, elevated fibrinogen or fibrin degradation products, and
thrombocytosis.80 Elevated fibrinogen and thrombocytosis are
the most common abnormalities, perhaps reflecting an over-
compensated form of intravascular coagulation.80 Levels of the
coagulation inhibitors antithrombin, protein C, and protein S
also may be reduced in malignancy.81
Markers of activated coagulation are elevated in the majority
of patients with solid tumors and leukemia.80 Fibrinopeptide A
levels reflect tumor activity, decreasing or increasing in response to
treatment or progression of disease, suggesting that tumor growth
and thrombin generation are intimately related.80 Furthermore,
these levels may fail to normalize after administration of heparin
to patients with cancer and DVT, perhaps explaining why these
DVTs may be refractory to anticoagulants.80
VTE is also associated with the treatment of some cancers.
DVT complicates 29% of general surgical procedures for
malignancy.81 Preoperative activation of the coagulation system,
as reflected by elevated thrombin-antithrombin complex values,
is associated with a 7.5-fold increased risk of postoperative
DVT.80 Some chemotherapeutic regimens also predispose to
DVT, and thrombotic complications may be as common as
the more widely recognized infectious complications.82 VTE
has been reported in up to 6% of patients undergoing treatment
for non-Hodgkin’s lymphoma, and in 17.5% of those receiving
therapy for breast cancer.83 Among patients with stage II breast
cancer, thrombosis was significantly more common in those
randomly assigned to 36 weeks of chemotherapy (8.8%) than
in those receiving only 12 weeks of treatment (4.9%).82 Potential
thrombogenic mechanisms associated with chemotherapy include
direct endothelial toxicity, induction of a hypercoagulable state,
reduced fibrinolytic activity, tumor cell lysis, and use of central
venous catheters.83,84 Some intravenous chemotherapeutic agents
are associated with activation of coagulation and increased
markers of thrombin generation, a response that is blocked by
pretreatment with heparin.85 An additional risk factor in some
cancer patients is an elevated soluble P-selectin.86
Surgery
The high incidence of postoperative DVT, as well as the avail-
ability of easily repeatable, noninvasive diagnostic tests, has
allowed a greater understanding of the risk factors associated
with surgery than in other conditions. Surgery constitutes a
spectrum of risk that is influenced by patient age, coexistent
thrombotic risk factors, type of procedure, extent of surgical
trauma, length of procedure, and duration of postoperative
immobilization.87 The type of surgical procedure is particularly
important.41 Historically, the overall incidence of DVT is
approximately 19% in patients undergoing general surgical
operations, 24% in those having elective neurosurgical proce-
dures; and 48%, 51%, and 61% among those undergoing surgery
for hip fracture, hip arthroplasty, and knee arthroplasty,
respectively.87 On the basis of these data, patients can be classified
as being at low, moderate, or high risk for thromboembolic
 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History
complications. Approximately half of postoperative lower
extremity thrombi develop in the operating room, with the
remainder occurring over the next 3 to 5 days.88 However, the
risk for development of DVT does not end uniformly at hospital
discharge. In one study, 51% of the thromboembolic events
occurred after discharge from gynecologic surgical procedures.89
Similarly, up to 25% of patients undergoing abdominal surgery
have DVT within 6 weeks of discharge.90 Heit and associates
found a nearly 22-fold higher risk of DVT and PE among
patients who were hospitalized following previous surgery.89
All components of the Virchow triad may be present in the
surgical patient—perioperative immobilization, transient changes
in coagulation and fibrinolysis, and the potential for gross venous
injury. Immobilization is associated with a reduction in venous
outflow and capacitance during the early postoperative period.91
Surgery is also accompanied by a transient, low-level hyperco-
agulable state, presumably mediated by the release of TF, which
is marked by a rise in thrombin activation markers shortly after
the procedure begins.91 The thrombogenic potential of different
surgical procedures appears to differ, with greater rises in
thrombin activation markers during hip arthroplasty than after
laparotomy.92 Increased levels of PAI–1 are also associated with
a decrease in fibrinolytic activity on the first postoperative day,
the “postoperative fibrinolytic shutdown.”93 This relationship
between impaired fibrinolysis and postoperative DVT may be
particularly important,64 with preoperative and early postopera-
tive elevations in PAI-1 correlating with the development of
thrombosis in orthopedic patients.93 Complications are also an
important trigger: in a large VA study involving more than
76,000 patients, the strongest predictors of postoperative VTE
included myocardial infarction, blood transfusion (>4 units),
and urinary tract infection.94
Trauma
The prevalence of DVT among autopsied trauma casualties has
been reported to be as high as 65%, comparable to the 58%
incidence among injured patients in modern venographic series.11
Substantially lower DVT rates, ranging from 4% to 20%,95
have been noted in series using duplex ultrasonography, although
many patients studied were receiving prophylaxis and the
limitations of ultrasound in screening asymptomatic patients
are well recognized. Recent trauma was associated with nearly
a 13-fold increase in risk.89
Although the risk of DVT may be less than 20% in some
injured patients,11 certain subgroups are at particularly high
risk. Age (OR, 1.05 for each 1-year increment), blood transfusion
(OR, 1.74), surgery (OR, 2.30), fracture of the femur or tibia
(OR, 4.82), and spinal cord injury (OR, 8.59) have been
significantly associated with the development of DVT in this
population.11 Other reported risk factors are a hospital stay
longer than 7 days,96 increased Injury Severity Score (ISS),96-98
pelvic fractures,99 major venous injury,100 presence of femoral
venous lines,101 the duration of immobilization,102 and prolonga-
tion of the partial thromboplastin time.103
As with postoperative DVT, several pathophysiologic elements
may be responsible for the high incidence of DVT in trauma
patients. Immobilization by skeletal fixation, paralysis, and
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1923
critical illness are associated with venous stasis, whereas mechani-
cal injury is important after direct venous trauma and central
venous cannulation. Less well appreciated is the hypercoagulable
state after depletion of coagulation inhibitors and components
of the fibrinolytic system. Fibrinopeptide A levels rise after
injury,104 consistent with activation of coagulation, whereas
fibrinolytic activity has been found to increase initially and
then decrease.105,106
Pregnancy
The incidence of VTE in the pregnant population is 6 to 10
times greater than matched controls107 and causes approximately
10% of all maternal deaths.108 Using clinical evaluation, VTE
has been reported at a rate of 1.3% to 7% during pregnancy
and 6.1% to 23% in the postpartum period.109 However,
studies that used venography, Doppler ultrasonography, or
ventilation-perfusion scans for evaluation of clinically suspected
thromboembolism have suggested an incidence of 0.029% to
0.055% in this population.110 The risk of thrombosis appears to
be two to three times greater during the puerperium, with the
highest incidence found after cesarean section.111 Interestingly,
when VTE has been objectively documented, the occurrence
of thrombosis is equally distributed throughout all three
trimesters.112
DVT in pregnancy has been attributed to impaired venous
outflow due to uterine compression because 97% of reported
thromboses have been isolated to the left leg.112 Furthermore,
pregnancy is associated with a transient hypercoagulable state
due to increases in the levels of fibrinogen, von Willebrand
factor, and factors II, VII, VIII, and X. Compounding this
acquired functional resistance to activated protein C is also
seen during pregnancy.113 Similarly, protein S levels are decreased
by 50% to 60% early during pregnancy, with free protein S
levels comparable with hereditary heterozygous protein S
deficiency.114,115 The fibrinolytic system is also altered in preg-
nancy: levels of tissue plasminogen activator (tPA) are decreased
and PAI-1 and PAI-2 increased.116
Both retrospective and prospective studies have demonstrated
that between 30% and 50% of women with a pregnancy-
associated VTE also have an inherited thrombophilia. This
high incidence has led to the recommendation of screening
for thrombophilia in those pregnant patients with a personal
or family history of VTE.117,118 The risk of puerperal DVT
also increases with maternal age, suppression of lactation,
hypertension, and assisted delivery but not with the number
of pregnancies.119
Oral Contraceptives and Hormonal Therapy
As suggested by case reports in the early 1960s, further studies
have now established the use of oral contraceptives as an
independent risk factor for the development of DVT. These
studies noted ORs of 3.8 to 11.0 for thrombosis,120 and an
unweighted summary relative risk among 18 controlled studies
was 2.9.121 Approximately one-quarter of apparently idiopathic
thromboembolic events among women of childbearing age have
1924 SECTION 22 Acute Venous Thromboembolic Disease
been attributed to oral contraceptives. Early studies also suggested
that thromboembolism is responsible for approximately 2% of
deaths in young women, with contraceptive-associated mortality
rates of 1.3 and 3.4 per 100,000 among women aged 20 to
34 and 35 to 44 years, respectively.122 The increased risk of
thromboembolism appears to diminish soon after oral contra-
ceptives are discontinued and is independent of the duration
of use.123
Risk is correspondingly higher when oral contraceptive use
is combined with other factors, such as surgery124 and inherited
inhibitor deficiencies.125 The factor V Leiden mutation may be
particularly important in this regard; resistance to activated
protein C has been reported in up to 30% of patients with
contraceptive-associated thromboembolism.126 The use of third-
generation oral contraceptives may act synergistically with the
factor V Leiden mutation, raising thromboembolic risk 30- to
50-fold.127-129
Estrogenic compounds also increase the risk of VTE when
used for lactation suppression119 in treatment of carcinoma of
the prostate and as postmenopausal replacement therapy.130
Although estrogen doses used for postmenopausal replacement
therapy are approximately one-sixth those in oral contraceptives,
some data support an increased thromboembolic risk at these
doses as well. Several studies show a twofold to fourfold higher
risk of VTE among women taking hormone replacement
therapy.130-134 This increased risk is greatest during the first year
of treatment.131,134 However, given the relative infrequency of
thromboembolism, this risk represents only one or two additional
cases of thromboembolism per year in every 10,000 women in
this age group.
Estrogen in pharmacologic doses is associated with alterations
in the coagulation system that may contribute to this thrombotic
tendency. Such alterations include decreases in PAI-1135 and
increases in blood viscosity, fibrinogen, plasma levels of factors
VII and X, and platelet adhesion and aggregation.136,137 An
associated prothrombotic state is implied by rises in markers
of activated coagulation occurring in conjunction with elevations
of circulating factor VIIa and decreases in antithrombin and
protein S inhibitor activity.136,138 The extent to which anti-
thrombin and protein S are depressed is significantly less with
lower-estrogen preparations.139
Blood Group
There also appears to be a relationship between VTE risk and
the ABO blood groups, with a higher prevalence of blood type
A and correspondingly lower prevalence of blood type O
groups.140,141 In reviewing the literature, Mourant and col-
leagues142 found the relative incidence of type A to be 1.41
times higher among patients with thromboembolism than among
controls. The effect of blood type was greater in young women
who were taking oral contraceptives or were pregnant; the relative
incidence of type A among patients with thromboembolism
was 3.12 in those taking oral contraceptives and 1.85 in those
who were pregnant. A relationship between soluble endothelial
cell markers and ABO blood group is known to exist, with
significantly lower levels of von Willebrand factor among those
with type O blood.143
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Geography and Ethnicity
There are also geographic differences in the frequency of VTE,
as the incidence of postoperative DVT in Europe has been
noted to be nearly twice that of North America.81,87 Higher
rates of thromboembolism have also been noted in the central
United States compared with either coast.144 Autopsy series
suggest that although the prevalence of thromboembolism is
identical among American black and white patients, it is sig-
nificantly higher than in a matched Ugandan black population.145
A similar autopsy series noted the prevalence of thromboem-
bolism to be 40.6% in Boston and 13.9% in Kyushu, Japan.146
Unfortunately, regional variations in underlying medical and
surgical conditions, as well as in prophylactic measures and
diagnostic methods, may confound any apparent differences
in the incidence of thromboembolism among different ethnic
and geographic groups. Nevertheless, it is certainly conceivable
that differences between ethnic groups might arise from either
genetic and/or environmental factors. Such differences seem
likely based on recognized geographic differences in the spectrum
of mutations leading to congenital anticoagulant deficiencies.147
Such theoretical concerns are also supported by geographic
variability in the incidence of the factor V Leiden mutation.
The factor V Leiden allele has a prevalence of 4.4% in Europeans,
corresponding to a carrier rate of 8.8%, but the allele has not
been identified in Southeast Asian or African populations.148
Inflammatory Bowel Disease
Clinical series have reported VTE to complicate inflammatory
bowel disease (IBD) in 1.2% to 7.1% of cases.149,150 Crohn
disease has incidence rates of 31.4/10,000 person-years and
10.3/10,000 person-years for DVT and PE, respectively.
Ulcerative colitis also has a high incident rate of 30.0/10,000
and 19.8/10,000 person-years for DVT and PE, respectively.
Such thromboses frequently occur among young patients, are
more common with active disease, and may affect unusual sites,
such as the cerebral veins.149,150 Greater extent of colonic disease
in ulcerative colitis portends a higher risk of VTE. Most cases
are not associated with inherited hypercoagulable states. However,
fibrinopeptide A elevations in IBD suggest that active inflam-
mation is associated with activation of coagulation, possibly
mediated by endotoxin-induced monocyte activation.149-151
Systemic Lupus Erythematosus
A syndrome of arterial and venous thrombosis, recurrent abor-
tion, thrombocytopenia, and neurologic disease may complicate
systemic lupus erythematosus (SLE) when accompanied by the
presence of antiphospholipid antibodies.152 Lupus anticoagulant
and anticardiolipin antibodies may be seen in association with
SLE; with other autoimmune disorders; with nonautoimmune
disorders, such as syphilis and acute infection, with drugs,
including chlorpromazine, procainamide, and hydralazine; and
with older age.153
Lupus anticoagulant is present in 34% of patients with SLE
and anticardiolipin antibodies in 44%, in comparison with 2%
and 0% to 7.5%, respectively, of the general population.153
 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History
Among patients with SLE, those with lupus anticoagulant are at
a sixfold higher risk for VTE, whereas those with anticardiolipin
antibodies are at a twofold greater risk.154 The incidence of arterial
or venous thrombosis is 25% in patients with lupus anticoagulant
and 28% in patients with anticardiolipin antibodies.153
Varicose Veins
Varicose veins are also included as a risk factor for acute DVT,
although frequently only as a marker of either previous venous
disease.155 Most studies evaluating thrombotic risk have been
performed in inpatients with other major risk factors for DVT.
Such studies have inconsistently supported varicose veins as a
risk factor in postoperative, post-stroke, or postmyocardial
infarction cases.155-157 The importance of varicose veins in
otherwise healthy outpatients with DVT has been questioned
by some researchers158 because varicose veins were not identified
as independent risk factor in young women,159 although some
studies of postmenopausal women have reported varicose veins
or superficial thrombophlebitis to be associated with ORs of
3.6 to 6.9 for the development of thromboembolism.131,134
However, Heit and associates160 found that varicose veins
were independent predictors of DVT. They also reported that
age is an important factor in these patients, reporting a higher
correlation between DVT and varicosity in young patients. For
example, 45-year-old patients with varicose veins had a fourfold
higher risk of VTE, 60-year-old patients had a twofold greater
risk, and 75-year-old patients had no increase in risk. This
group also found that patients with previous superficial vein
thrombosis were more than four times more likely to have DVT
or PE.160 See Chapter 150.
Iliac Vein Compression
The association of VTE and anatomic anomalies or syndromes
represents a congenital risk factor responsible for DVT in both
the upper and lower extremities. Left iliac vein compression by
the right iliac artery and fifth lumbar artery was first described
by May and Thurner in cadavers who hypothesized that chronic
pulsation of the right iliac artery and mechanical obstruction
led to intimal hypertrophy of the vein wall and subsequent
venous obstruction.161 In actuality, it was Virchow who had
initially observed iliofemoral vein thrombosis was five times
more likely to occur in the left leg than in the right leg over
a century earlier.162 Although left lower extremity venous
hypertension associated with or without left iliofemoral DVT
has come to be known as May-Thurner syndrome, it is impor-
tant to recognize, if only for historical nomenclature, that a
similar syndrome was described by Cockett in 1965 (Cockett
syndrome) and took popularity over the term May-Thurner
syndrome in Europe. However, it was Cockett who associated
the acute phase of iliofemoral DVT secondary to compression
of the iliac vein with the long-term consequence of chronic
venous insufficiency (CVI). In addition, it was Cockett who
noted surgical intervention for the purpose of alleviating the
skin ulcers and varicosities associated with iliac vein compres-
sion was ineffective unless the underlying disease process was
identified.163
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1925
May-Thurner syndrome is more common in young to
middle-aged women, especially after multiple pregnancies. The
presenting symptom is often acute onset of left leg pain and
swelling secondary to thrombosis. Atypically, patients may present
with symptoms of CVI that are unresponsive to compression
stockings, leg elevation, and a calf exercise program.164 Early
20th century postmortem dissections revealed a 22% to 32%
incidence of left iliac vein compression.165 Modern computed
tomography imaging has revealed that in an asymptomatic
population, the average amount of compression on the left
iliac vein was 35%, and 24% of this population demonstrated
greater than 50% compression.165 Although individuals in such
series were asymptomatic, the incidence of symptomatic left
common iliac vein compression presenting with either edema
or DVT is estimated to be between 37% and 61%.166,167
Interestingly, the presence of an abdominal aortic aneurysm
was associated with a significantly less amount of compres-
sion on the left common iliac vein by the right common iliac
artery secondary to a higher prevalence of tortuosity in that
artery.168
Popliteal Vein Entrapment
Although arterial entrapment syndrome is well described in
the literature, popliteal vein entrapment has been reported to
occur either alone or with the artery in 10% of cases.169 Anatomic
anomalies of the medial head of the gastrocnemius have been
associated with popliteal vascular entrapment. However, when
venous entrapment occurs in a setting without arterial entrap-
ment, both the medial or the lateral head of the gastrocnemius
have been shown to contribute.170 Bony tumors and hypertro-
phied fibrous fascia have also been associated with isolated
venous involvement.171,172 Traditionally, popliteal artery entrap-
ment has been more associated with the male gender; venous
entrapment has been reported to occur 70% of the time in
females.173 The presentation is often that of a young adult with
signs of CVI, including leg swelling varicosities, skin changes,
and DVT.
Other Risk Factors
Risk factors for VTE covered in other sections in this book
include inherited thrombophilias (Chapter 38), thoracic outlet
syndrome (Chapter 123), central venous catheters (Chapter
149), and inferior vena cava anomalies (Chapter 163). Traditional
risk factors for VTE have included obesity and cardiac disease;
however, the evidence supporting these risk factors remains
equivocal. Among postmenopausal women, a body mass index
of greater than 25 to 30 kg/m2 has been associated with a
significantly increased risk of VTE.132,134 Some investigators
have reported obesity to be associated with a twofold greater
risk for postoperative DVT, although multivariate analyses by
others has not shown obesity to constitute an independent
risk.155 Obesity (and past tobacco smoking) was not an inde-
pendent risk factor of DVT in the Olmsted County study160
and has not been proven to be a risk factor for the development
of DVT after stroke.157 However, obesity is a risk factor for
recurrent DVT.174
1926 SECTION 22 Acute Venous Thromboembolic Disease
Systemic hypercoagulability, congestive heart failure, and
enforced bed rest may predispose patients who are hospitalized
with acute myocardial infarction to DVT. The incidence of DVT
in this population has been reported to be 20% to 40%.87,156,175
Some investigators have noted the incidence of DVT to be higher
among patients in whom myocardial infarction was confirmed
(34%) than in those in whom the diagnosis was excluded (7%).
The prevalence of PE among autopsied patients has also not
differed substantially from that in other inpatients.144,145
Although MI as a risk factor may be in question, those older
than 60 years with congestive heart failure have a DVT rate of
54%.176 However, the evidence supporting congestive heart
failure as an independent risk factor for DVT is also conflicting.
A variety of thromboembolic complications account for nearly
half the deaths among patients who did not undergo anticoagula-
tion after hospitalization for congestive heart failure, but conges-
tive heart failure has not been identified as an independent risk
factor for postoperative DVT. The balance of evidence suggests
that severely ill medical patients are at significant risk for VTE,177
although it is difficult to define the additional risk associated
with cardiac disease.
NATURAL HISTORY
The relative balance between organization, thrombolysis, propaga-
tion, and rethrombosis determines outcomes after human throm-
bosis. From a clinical perspective, the most important events
after thrombosis are recanalization and recurrent thrombosis.
Recanalization
Impedance plethysmography was the first widely available
noninvasive test permitting serial evaluations of outflow obstruc-
tion due to an acute DVT. Although this test could not dis-
tinguish between recanalization and the development of collateral
venous outflow, results of such studies were found to normalize
in 67% of patients by 3 months and in 92% of patients by 9
months.178 Venous duplex ultrasonography allows individual
venous segments to be observed over time and has further
documented that recanalization does occur in most patients
after acute DVT. In 21 patients monitored prospectively with
duplex scanning, recanalization occurred in 44% of patients at
7 days and in 100% of patients by 90 days after the acute
event.179 Several additional studies180,181 confirm the histologic
findings that recanalization begins early after an acute DVT,
with the greatest reduction in thrombus load occurring within
3 months of the event. Complete thrombus resolution has been
reported in 56% of patients monitored for 9 months.179,182
However, recanalization may continue for months to years after
the acute event.181
Recurrent Venous Thrombosis
Nearly 30% of patients will develop a recurrence within a 10-year
time span.183 Recurrences are more likely with the same event
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type as the incident event; for example, those who initially
developed a PE are more likely to develop another PE instead
of a DVT.184 Independent predictors for recurrent DVT include
increasing age, obesity, malignant neoplasm, and extremity
paresis. In a series of landmark trials, among patients with
proximal DVT, recurrent thromboembolic events were found
in 5.2% of patients treated with standard anticoagulation for
3 months, compared with 47% of patients treated with a
3-month course of low-dose subcutaneous heparin.185,186
Despite the significance of these observations, reports of
serial noninvasive follow-up examinations suggest that these
studies may underestimate the incidence of new thrombotic
events. In a series of 177 patients, most of whom were treated
with standard anticoagulation measures, recurrent thrombotic
events were observed in 52% of patients.187 New thrombi were
observed in 6% of uninvolved contralateral extremities, whereas
propagation of thrombi to new segments occurred in 30% of
involved limbs and rethrombosis of a partially occluded or
recanalized segment in 31% of extremities. Propagation in the
ipsilateral limb tended to occur as an early event at a median
of less than 40 days after presentation, whereas rethrombosis
and extension to the contralateral limb tended to occur sporadi-
cally as late events.
Mortality
The severity of PE is shown in 30-year autopsy studies, which
demonstrated a 26% incidence of PE in hospitalized patients,
of which 9% was fatal. This translates to a 1% incidence of PE
and a 0.36% incidence of death from PE in all hospitalized
patients per year.188 See Chapter 151.
SELECTED KEY REFERENCES
Heit JA, Cohen AT, Anderson FJ. Estimated annual number of incident
and recurrent, non-fatal venous thromboembolism (VTE) events
in the US. Blood. 2005;106(11):267A.
Data on the incidence and prevalence of VTE taken from the Rochester
community.
Meissner MH, Caps MT, Bergelin RO, Manzo RA, Strandness DE
Jr. Propagation, rethrombosis and new thrombus formation after
acute deep venous thrombosis. J Vasc Surg. 1995;22(5):558–567.
This study uses careful serial ultrasound studies to determine the rate of
thrombus extension/progression and rethrombosis.
Rosendaal FR. Thrombosis in the young: epidemiology and risk factors.
A focus on venous thrombosis. Thromb Haemost. 1997;78(1):1–6.
Study identifies the effect of age on thrombosis, and the fact that the younger
the patient, the more risk factors are necessary to precipitate thrombosis.
A complete reference list can be found online at www.expertconsult.com.
 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History
REFERENCES
1. Hull RD, Raskob GE, Hirsh J. Prophylaxis of venous throm-
boembolism. An overview. Chest. 1986;89(5 suppl):374S–383S.
2. Biland L, Widmer LK. Varicose veins (VV) and chronic venous
insufficiency (CVI). Medical and socio-economic aspects, Basle
study. Acta Chir Scand Suppl. 1988;544:9–11.
3. Coon WW, Willis PW 3rd, Keller JB. Venous thromboembolism
and other venous disease in the Tecumseh community health
study. Circulation. 1973;48(4):839–846.
4. Silva Mde C. Chronic venous insufficiency of the lower limbs and
its socio-economic significance. Int Angiol. 1991;10(3):152–157.
5. Wakefield TW, et al. Call to action to prevent venous throm-
boembolism. J Vasc Surg. 2009;49(6):1620–1623.
6. Heit JA, Cohen AT, Anderson FJ. Estimated annual number
of incident and recurrent, non-fatal venous thromboembolism
(VTE) events in the US. Blood. 2005;106(11).
7. Heit JA, Petterson TM, Farmer SA, Bailey KR, Melton LJ.
Trends in the incidence of deep vein thrombosis and pulmonary
embolism: a 35-year population based study. Blood. 2006;108:
403a.
8. Heit JA. The epidemiology of venous thromboembolism in the
community. Arterioscler Thromb Vasc Biol. 2008;28(3):370–372.
9. Keenan CR, White RH. The effects of race/ethnicity and sex
on the risk of venous thromboembolism. Curr Opin Pulm Med.
2007;13(5):377–383.
10. Cohen AT, et al. Venous thromboembolism (VTE) in Europe. The
number of VTE events and associated morbidity and mortality.
Thromb Haemost. 2007;98(4):756–764.
11. Geerts WH, et al. A prospective study of venous thromboembo-
lism after major trauma. N Engl J Med. 1994;331(24):1601–1606.
12. Obi AT, et al. Validation of the caprini venous thromboembolism
risk assessment model in critically ill surgical patients. JAMA
Surg. 2015;150(10):941–948.
13. Cook DJ, et al. Prevalence, incidence, and risk factors for venous
thromboembolism in medical-surgical intensive care unit patients.
J Crit Care. 2005;20(4):309–313.
14. Muscedere JG, Heyland DK, Cook D. Venous thromboembolism
in critical illness in a community intensive care unit. J Crit Care.
2007;22(4):285–289.
15. Liebson CL, et al. Risk factors for venous thromboembolism
in nursing home residents. Mayo Clin Proc. 2008;83(2):151–
157.
16. Attia J, et al. Deep vein thrombosis and its prevention in critically
ill adults. Arch Intern Med. 2001;161(10):1268–1279.
17. Azarbal A, et al. Duplex ultrasound screening detects high rates
of deep vein thromboses in critically ill trauma patients. J Vasc
Surg. 2011;54(3):743–747. discussion 747–748.
18. Kakkar VV, et al. Natural history of postoperative deep-vein
thrombosis. Lancet. 1969;2:230–232.
19. Cogo A, et al. Acquired risk factors for deep-vein thrombosis in
symptomatic outpatients. Arch Intern Med. 1994;154(2):164–
168.
20. Oger E, et al. The value of a risk factor analysis in clinically sus-
pected deep venous thrombosis. Respiration. 1997;64(5):326–330.
21. Anderson FA Jr, et al. The prevalence of risk factors for venous
thromboembolism among hospital patients. Arch Intern Med.
1992;152(8):1660–1664.
22. Wakefield THP. Complications in Surgery. 2nd ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2011.
23. Nordstrom M, et al. A prospective study of the incidence of
deep-vein thrombosis within a defined urban population. J Intern
Med. 1992;232(2):155–160.
24. Rosendaal FR. Thrombosis in the young: epidemiology and
risk factors. A focus on venous thrombosis. Thromb Haemost.
1997;78(1):1–6.
Downloaded for Nadiah An-Nur (nadiahnnr3@gmail.com) at Universitas Muslim Indonesia from ClinicalKey.com by Elsevier on October 16, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
1926.e1
25. Hansson PO, et al. Deep vein thrombosis and pulmonary
embolism in the general population. ‘The Study of Men Born
in 1913’. Arch Intern Med. 1997;157(15):1665–1670.
26. Tardy B, et al. Effects of long travels in sitting position in elderly
volunteers on biological markers of coagulation activation and
fibrinolysis. Thromb Res. 1996;83(2):153–160.
27. Gibbs NM. Venous thrombosis of the lower limbs with particular
reference to bed-rest. Br J Surg. 1957;45(191):209–236.
28. McLachlin AD, et al. Venous stasis in the lower extremities.
Ann Surg. 1960;152:678–685.
29. Rohrer MJ, et al. A prospective study of the incidence of
deep venous thrombosis in hospitalized children. J Vasc Surg.
1996;24(1):46–49, discussion 50.
30. Sandoval JA, et al. Incidence, risk factors, and treatment patterns
for deep venous thrombosis in hospitalized children: An increasing
population at risk. J Vasc Surg. 2008;47(4):837–843.
31. Buck JR, et al. Pulmonary embolism in children. J Pediatr Surg.
1981;16(3):385–391.
32. Coon WW. Epidemiology of venous thromboembolism. Ann
Surg. 1977;186(2):149–164.
33. Wise RC, Todd JK. Spontaneous, lower-extremity venous
thrombosis in children. Am J Dis Child. 1973;126(6):766–769.
34. Leslie IJ, et al. A prospective study of deep vein thrombosis of
the leg in children on halo-femoral traction. J Bone Joint Surg
Br. 1981;63-B(2):168–170.
35. DeAngelis GA, et al. Prevalence of deep venous thrombosis in
the lower extremities of children in the intensive care unit.
Pediatr Radiol. 1996;26(11):821–824.
36. McBride WJ, et al. Pulmonary embolism in pediatric trauma
patients. J Trauma. 1994;37(6):913–915.
37. Radecki RT, Gaebler-Spira D. Deep vein thrombosis in
the disabled pediatric population. Arch Phys Med Rehabil.
1994;75(3):248–250.
38. Nguyen LT, et al. Spontaneous deep vein thrombosis in childhood
and adolescence. J Pediatr Surg. 1986;21(7):640–643.
39. Bernstein D, Coupey S, Schonberg SK. Pulmonary embolism
in adolescents. Am J Dis Child. 1986;140(7):667–671.
40. DeAngelis GA, et al. Prevalence of deep venous thrombosis in
the lower extremities of children in the intensive care unit.
Pediatr Radiol. 1996;26:821–824.
41. Sigel B, Ipsen J, Felix WR Jr. The epidemiology of lower
extremity deep venous thrombosis in surgical patients. Ann
Surg. 1974;179(3):278–290.
42. Warlow C, Ogston D, Douglas AS. Deep venous thrombosis of
the legs after strokes. Part I–incidence and predisposing factors.
Br Med J. 1976;1:1178–1181.
43. Heit JA, et al. Risk factors for deep vein thrombosis and
pulmonary embolism: a population-based case-control study.
Arch Intern Med. 2000;160(6):809–815.
44. Cruickshank JM, Gorlin R, Jennett B. Air travel and throm-
botic episodes: the economy class syndrome. Lancet. 1988;
2:497–498.
45. Homans J. Thrombosis of the deep leg veins due to prolonged
sitting. N Engl J Med. 1954;250(4):148–149.
46. Ledermann JA, Keshavarzian A. Acute pulmonary embolism
following air travel. Postgrad Med J. 1983;59:104–105.
47. Thromboembolism and air travel. Lancet. 1988;2(8614):797.
48. Sarvesvaran R. Sudden natural deaths associated with commercial
air travel. Med Sci Law. 1986;26(1):35–38.
49. Symington I, Stack BHR. Pulmonary thromboembolism after
travel. Br J Dis Chest. 1977;71:147.
50. Wessler S. Thrombosis in the presence of vascular stasis. Am J
Med. 1962;33:648–666.
51. Landgraf H, et al. Economy class syndrome: rheology, fluid
balance, and lower leg edema during a simulated 12-hour long
distance flight. Aviat Space Environ Med. 1994;65(10 Pt 1):
930–935.
1926.e2 SECTION 22 Acute Venous Thromboembolic Disease
52. Ferrari E, et al. Travel as a risk factor for venous thrombo-
embolic disease: a case-control study. Chest. 1999;115(2):440–
444.
53. Samama MM. An epidemiologic study of risk factors for deep
vein thrombosis in medical outpatients: the Sirius study. Arch
Intern Med. 2000;160(22):3415–3420.
54. Scurr JH, et al. Frequency and prevention of symptomless
deep-vein thrombosis in long-haul flights: a randomised trial.
Lancet. 2001;357(9267):1485–1489.
55. Lapostolle F, et al. Severe pulmonary embolism associated with
air travel. N Engl J Med. 2001;345(11):779–783.
56. Paganin F, et al. Venous thromboembolism in passengers following
a 12-h flight: a case-control study. Aviat Space Environ Med.
2003;74(12):1277–1280.
57. Belcaro G, et al. Venous thromboembolism from air travel: the
LONFLIT study. Angiology. 2001;52(6):369–374.
58. Eklof B. Air travel related venous thromboembolism–an existing
problem that can be prevented? Cardiovasc Surg. 2002;10(2):
95–97.
59. Piccioli A, Prandoni P, Goldhaber SZ. Epidemiologic charac-
teristics, management, and outcome of deep venous thrombosis
in a tertiary-care hospital: the Brigham and Women’s Hospital
DVT registry. Am Heart J. 1996;132(5):1010–1014.
60. Sevitt S. The vascularisation of deep-vein thrombi and their
fibrous residue: a post mortem angio-graphic study. J Pathol.
1973;111(1):1–11.
61. Simioni P, et al. The risk of recurrent venous thromboembolism
in patients with an Arg506→Gln mutation in the gene for factor
V (factor V Leiden). N Engl J Med. 1997;336(6):399–403.
62. De Stefano V, et al. The risk of recurrent deep venous throm-
bosis among heterozygous carriers of both factor V Leiden
and the G20210A prothrombin mutation. N Engl J Med.
1999;341(11):801–806.
63. den Heijer M, et al. Is hyperhomocysteinaemia a risk factor for
recurrent venous thrombosis? Lancet. 1995;345:882–885.
64. Prins MH, Hirsh J. A critical review of the evidence supporting
a relationship between impaired fibrinolytic activity and venous
thromboembolism. Arch Intern Med. 1991;151(9):1721–1731.
65. Bergqvist D, et al. Venous thromboembolism and cancer. Curr
Probl Surg. 2007;44(3):157–216.
66. Shen VS, Pollak EW. Fatal pulmonary embolism in cancer
patients: is heparin prophylaxis justified? South Med J. 1980;73(7):
841–843.
67. Cornuz J, et al. Importance of findings on the initial evaluation
for cancer in patients with symptomatic idiopathic deep venous
thrombosis. Ann Intern Med. 1996;125(10):785–793.
68. Prandoni P, et al. Deep-vein thrombosis and the incidence of
subsequent symptomatic cancer. N Engl J Med. 1992;327(16):
1128–1133.
69. Monreal M, et al. Occult cancer in patients with deep venous
thrombosis. A systematic approach. Cancer. 1991;67(2):541–545.
70. Griffin MR, et al. Deep venous thrombosis and pulmonary
embolism. Risk of subsequent malignant neoplasms. Arch Intern
Med. 1987;147(11):1907–1911.
71. Nordstrom M, et al. Deep venous thrombosis and occult
malignancy: an epidemiological study. BMJ. 1994;308:891–894.
72. Sorensen HT, et al. The risk of a diagnosis of cancer after primary
deep venous thrombosis or pulmonary embolism. N Engl J Med.
1998;338(17):1169–1173.
73. Khorana AA, et al. Frequency, risk factors, and trends for venous
thromboembolism among hospitalized cancer patients. Cancer.
2007;110(10):2339–2346.
74. Winter PC. The pathogenesis of venous thromboembolism in
cancer: emerging links with tumour biology. Hematol Oncol.
2006;24(3):126–133.
75. Osborne N, Wakefield TW, Henke PK, Venous thromboembolism
in cancer patients undergoing major surgery. Ann Surg Oncol.
2008;15(12):3567–3578.
Downloaded for Nadiah An-Nur (nadiahnnr3@gmail.com) at Universitas Muslim Indonesia from ClinicalKey.com by Elsevier on October 16, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
76. Prandoni P, Falanga A, Piccioli A. Cancer and venous throm-
boembolism. Lancet Oncol. 2005;6(6):401–410.
77. Nijziel MR, et al. From Trousseau to angiogenesis: the link
between the haemostatic system and cancer. Neth J Med. 2006;
64(11):403–410.
78. Rickles FR, Falanga A. Molecular basis for the relationship between
thrombosis and cancer. Thromb Res. 2001;102(6):V215–V224.
79. Nachman RL, et al. Interleukin 1 induces endothelial cell synthesis
of plasminogen activator inhibitor. J Exp Med. 1986;163(6):
1595–1600.
80. Falanga A, et al. Hemostatic system activation in patients with
lupus anticoagulant and essential thrombocythemia. Semin
Thromb Hemost. 1994;20:324–327.
81. Clagett GP, Reisch JS. Prevention of venous thromboembolism
in general surgical patients. Results of meta-analysis. Ann Surg.
1988;208:227–240.
82. Levine MN, et al. The thrombogenic effect of anticancer drug
therapy in women with stage II breast cancer. N Engl J Med.
1988;318:404–407.
83. Doll DC, Ringenberg QS, Yarbro JW. Vascular toxicity associated
with antineoplastic agents. J Clin Oncol. 1986;4:1405–1417.
84. Clarke C, Otridge B, Carney D. Thromboembolism. A complica-
tion of weekly chemotherapy in the treatment of non-Hodgkin’s
lymphoma. Cancer. 1990;66(9):2027–2030.
85. Edwards RL, et al. Abnormalities of blood coagulation
tests in patients with cancer. Am J Clin Pathol. 1987;88:596–602.
86. Ay C, et al. High plasma levels of soluble P-selectin are predictive
of venous thromboembolism in cancer patients: results from
the Vienna Cancer and Thrombosis Study (CATS). Blood.
2008;112(7):2703–2708.
87. Clagett GP, et al. Prevention of venous thromboembolism. Chest.
1995;108(4 suppl):312S–334S.
88. Kakkar VV, et al. Deep vein thrombosis of the leg. Is there a
“high risk” group? Am J Surg. 1970;120(4):527–530.
89. Heit JA, et al. Risk factors for deep vein thrombosis and
pulmonary embolism: a population-based case-control study.
Arch Intern Med. 2000;160:809–815.
90. Scurr JH, et al. Frequency and prevention of symptomless
deep-vein thrombosis in long-haul flights: a randomised trial.
Lancet. 2001;357:1485–1489.
91. Kambayashi J, et al. Activation of coagulation and fibrinolysis
during surgery, analyzed by molecular markers. Thromb Res.
1990;60(2):157–167.
92. Sharrock NE, et al. The John Charnley Award. Thrombo-
genesis during total hip arthroplasty. Clin Orthop Relat Res.
1995;319:16–27.
93. Kluft C, et al. The postoperative fibrinolytic shutdown: a rapidly
reverting acute phase pattern for the fast-acting inhibitor of
tissue-type plasminogen activator after trauma. Scand J Clin
Lab Invest. 1985;45:605–610.
94. Gangireddy C, et al. Risk factors and clinical impact of post-
operative symptomatic venous thromboembolism. J Vasc Surg.
2007;45(2):335–341, discussion 341-2.
95. Burns GA, et al. Prospective ultrasound evaluation of venous
thrombosis in high-risk trauma patients. J Trauma. 1993;
35:405–408.
96. Knudson MM, et al. Prevention of venous thromboembolism
in trauma patients. J Trauma. 1994;37(3):480–487.
97. Napolitano LM, et al. Asymptomatic deep venous thrombosis in
the trauma patient: is an aggressive screening protocol justified?
J Trauma. 1995;39(4):651–657, discussion 657-9.
98. Hill SL, Berry RE, Ruiz AJ. Deep venous thrombosis in the
trauma patient. Am Surg. 1994;60(6):405–408.
99. Knudson MM, et al. Thromboembolism following multiple
trauma. J Trauma. 1992;32(1):2–11.
100. Sue LP, Davis JW, Parks SN. Iliofemoral venous injuries: an
indication for prophylactic caval filter placement. J Trauma.
1995;39:693–695.
 CHAPTER 145  Acute Deep Venous Thrombosis: Epidemiology and Natural History
101. Knudson MM, et al. Use of low molecular weight heparin in
preventing thromboembolism in trauma patients. J Trauma.
1996;41(3):446–459.
102. Knudson MM, et al. Prevention of venous thromboembolism
in trauma patients. J Trauma. 1994;37(8083913):480–487.
103. Burns GA, et al. Prospective ultrasound evaluation of venous
thrombosis in high-risk trauma patients. J Trauma. 1993;35(3):
405–408.
104. Gando S, Tedo I, Kubota M. Posttrauma coagulation and
fibrinolysis. Crit Care Med. 1992;20:594–600.
105. Garcia Frade LJ, et al. Changes in fibrinolysis in the intensive
care patient. Thromb Res. 1987;47:593–599.
106. Kapsch DN, et al. Fibrinolytic response to trauma. Surgery.
1984;95:473–478.
107. Kujovich JL. Hormones and pregnancy: thromboembolic risks
for women. Br J Haematol. 2004;126(4):443–454.
108. James AH. Prevention and management of venous thromboem-
bolism in pregnancy. Am J Med. 2007;120(10 suppl 2):S26–S34.
109. Friederich PW, et al. Frequency of pregnancy-related venous
thromboembolism in anticoagulant factor-deficient women: impli-
cations for prophylaxis. Ann Intern Med. 1996;125(12):955–960.
110. Rutherford SMM, McGehee W, Strong T. Thromboembolic
disease associated with pregnancy: an 11-year review. Am J Obstet
Gynecol. 1991;164S:286.
111. Bates SM, et al. Use of antithrombotic agents during pregnancy:
the Seventh ACCP Conference on Antithrombotic and Throm-
bolytic Therapy. Chest. 2004;126:644.
112. Ginsberg JS, et al. Venous thrombosis during pregnancy: leg and
trimester of presentation. Thromb Haemost. 1992;67(5):519–520.
113. Eldor A. Thrombophilia and its treatment in pregnancy. J Thromb
Thrombolysis. 2001;12:23–30.
114. Malm J, Laurell M, Dahlback B. Changes in the plasma levels
of vitamin K-dependent proteins C and S and of C4b-binding
protein during pregnancy and oral contraception. Br J Haematol.
1988;68(4):437–443.
115. Alving BM, Comp PC. Recent advances in understanding clotting
and evaluating patients with recurrent thrombosis. Am J Obstet
Gynecol. 1992;167:1184–1191.
116. Brenner B. Haemostatic changes in pregnancy. Thromb Res.
2004;114(5–6):409–414.
117. Harvey D, Lowe GM. Factor V Leiden: association with venous
thromboembolism in pregnancy and screening issues. Br J Biomed
Sci. 2004;61(3):157–164.
118. McColl MD, et al. Risk factors for pregnancy associated venous
thromboembolism. Thromb Haemost. 1997;78:1183–1188.
119. Tindall VR. Factors influencing puerperal thrombo-embolism.
J Obstet Gynaecol Br Commonw. 1968;75:1324–1327.
120. Prandoni P, et al. Symptomatic deep-vein thrombosis and the post-
thrombotic syndrome. Haematologica. 1995;80(2 suppl):42–48.
121. Koster T, et al. Oral contraceptives and venous thromboembolism:
a quantitative discussion of the uncertainties. J Intern Med.
1995;238:31–37.
122. Inman WH, Vessey MP. Investigation of deaths from pulmonary,
coronary, and cerebral thrombosis and embolism in women of
child-bearing age. Br Med J. 1968;2:193–199.
123. Rees DC, Cox M, Clegg JB. World distribution of factor V
Leiden. Lancet. 1995;346:1133–1134.
124. Greene GR, Sartwell PE. Oral contraceptive use in patients with
thromboembolism following surgery, trauma, or infection. Am
J Public Health. 1972;62(5):680–685.
125. Pabinger I, Schneider B. Thrombotic risk of women with
hereditary antithrombin III-, protein C- and protein S-deficiency
taking oral contraceptive medication. The GTH Study Group
on Natural Inhibitors. Thromb Haemost. 1994;71:548–552.
126. Hellgren M, Svensson PJ, Dahlback B. Resistance to activated
protein C as a basis for venous thromboembolism associated
with pregnancy and oral contraceptives. Am J Obstet Gynecol.
1995;173(1):210–213.
Downloaded for Nadiah An-Nur (nadiahnnr3@gmail.com) at Universitas Muslim Indonesia from ClinicalKey.com by Elsevier on October 16, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
1926.e3
127. Bloemenkamp KW, et al. Enhancement by factor V Leiden
mutation of risk of deep-vein thrombosis associated with oral
contraceptives containing a third-generation progestagen. Lancet.
1995;346:1593–1596.
128. Helmerhorst FM, et al. Oral contraceptives and thrombotic
disease: risk of venous thromboembolism. Thromb Haemost.
1997;78:327–333.
129. Vandenbroucke JP, et al. Third-generation oral contraceptive and
deep venous thrombosis: from epidemiologic controversy to new
insight in coagulation. Am J Obstet Gynecol. 1997;177:887–891.
130. Grodstein F, et al. Prospective study of exogenous hormones
and risk of pulmonary embolism in women. Lancet. 1996;
348:983–987.
131. Varas-Lorenzo C, et al. Hormone replacement therapy and
the risk of hospitalization for venous thromboembolism: a
population-based study in southern Europe. Am J Epidemiol.
1998;147:387–390.
132. Jick H, et al. Risk of hospital admission for idiopathic venous
thromboembolism among users of postmenopausal oestrogens.
Lancet. 1996;348:981–983.
133. Daly E, et al. Case-control study of venous thromboembolism risk
in users of hormone replacement therapy. Lancet. 1996;348:1027.
134. Perez Gutthann S, et al. Hormone replacement therapy and
risk of venous thromboembolism: population based case-control
study. BMJ. 1997;314:796–800.
135. Scarabin PY, et al. Changes in haemostatic variables induced by
oral contraceptives containing 50 micrograms or 30 micrograms
oestrogen: absence of dose-dependent effect on PAI-1 activity.
Thromb Haemost. 1995;74:928–932.
136. Quehenberger P, et al. Increased levels of activated factor VII
and decreased plasma protein S activity and circulating throm-
bomodulin during use of oral contraceptives. Thromb Haemost.
1996;76:729–734.
137. Von Kaulla E, et al. Antithrombin 3 depression and thrombin
generation acceleration in women taking oral contraceptives.
Am J Obstet Gynecol. 1971;109:868–873.
138. Winkler UH, et al. Ethinylestradiol 20 versus 30 micrograms
combined with 150 micrograms desogestrel: a large comparative
study of the effects of two low-dose oral contraceptives on the
hemostatic system. Gynecol Endocrinol. 1996;10:265–271.
139. Blann AD, Daly RJ, Amiral J. The influence of age, gender
and ABO blood group on soluble endothelial cell markers and
adhesion molecules. Br J Haematol. 1996;92:498–500.
140. Nordstrom M, et al. A prospective study of the incidence of
deep-vein thrombosis within a defined urban population. J Intern
Med. 1992;232(2):155–160.
141. Wautrecht JC, et al. The role of ABO blood groups in the incidence
of deep vein thrombosis. Thromb Haemost. 1998;79:688–689.
142. Mourant AE, Kopec AC, Domaniewska-Sobczak K. Blood-groups
and blood-clotting. Lancet. 1971;1:223–227.
143. Blann AD, Daly RJ, Amiral J. The influence of age, gender
and ABO blood group on soluble endothelial cell markers and
adhesion molecules. Br J Haematol. 1996;92(2):498–500.
144. Kniffin WD, et al. The epidemiology of diagnosed pulmonary
embolism and deep venous thrombosis in the elderly. Arch Intern
Med. 1994;154:861–866.
145. Thomas WA, et al. Incidence of myocardial infarction correlated
with venous and pulmonary thrombosis and embolism. A
geographic study based on autopsies in Uganda. East Africa
and St. Louis, U.S.A. Am J Cardiol. 1960;5:41–47.
146. Gore I, Hirst AE, Tanaka K. Myocardial infarction and throm-
boembolism: a comparative study in Boston and in Kyushu,
Japan. Arch Intern Med. 1964;113:323–330.
147. Aiach M, Gandrille S, Emmerich J. A review of mutations causing
deficiencies of antithrombin, protein C and protein S. Thromb
Haemost. 1995;74:81–89.
148. Rees DC, Cox M, Clegg JB. World distribution of factor V
Leiden. Lancet. 1995;346:1133–1134.
1926.e4 SECTION 22 Acute Venous Thromboembolic Disease
149. Koenigs KP, McPhedran P, Spiro HM. Thrombosis in
inflammatory bowel disease. J Clin Gastroenterol. 1987;9:627–
631.
150. Jackson LM, et al. Thrombosis in inflammatory bowel disease:
clinical setting, procoagulant profile and factor V Leiden. QJM.
1997;90(3):183–188.
151. Vecchi M, et al. Risk of thromboembolic complications in
patients with inflammatory bowel disease. Study of hemostasis
measurements. Int J Clin Lab Res. 1991;21:165–170.
152. Hughes GR, Harris NN, Gharavi AE. The anticardiolipin
syndrome. J Rheumatol. 1986;13:486–489.
153. Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin
and the lupus anticoagulant in systemic lupus erythematosus
(SLE) and in non-SLE disorders. Prevalence and clinical sig-
nificance. Ann Intern Med. 1990;112:682–698.
154. Wahl DG, et al. Risk for venous thrombosis related to
antiphospholipid antibodies in systemic lupus erythematosus–a
meta-analysis. Lupus. 1997;6:467–473.
155. Nicolaides AN, et al. The origin of deep vein thrombosis: a
venographic study. Br J Radiol. 1971;44:653–663.
156. Maurer BJ, Wray R, Shillingford JP. Frequency of venous throm-
bosis after myocardial infarction. Lancet. 1971;2:1385–1387.
157. Warlow C, Ogston D, Douglas AS. Deep venous thrombosis
of the legs after strokes: Part 2-Natural history. Br Med J.
1976;1:1181–1183.
158. Campbell B. Thrombosis, phlebitis, and varicose veins. BMJ.
1996;312:198–199.
159. Vessey MP, Doll R. Oral contraceptives and thromboembolic
disease. Br Med J. 1968;2:696.
160. Heit JA, et al. The epidemiology of venous thromboembolism
in the community. Thromb Haemost. 2001;86:452–463.
161. May R, Thurner J. The cause of the predominantly sinistral
occurrence of thrombosis of the pelvic veins. Angiology. 1957;8(5):
419–427.
162. Virchow R. Uber die erwiterung kleiner Degasse. Arch Pathol
Antol. 1851;3:427.
163. Cockett FB, Thomas ML. The iliac compression syndrome. Br
J Surg. 1965;52:816–821.
164. Knipp BS, et al. Factors associated with outcome after interven-
tional treatment of symptomatic iliac vein compression syndrome.
J Vasc Surg. 2007;46:743–749.
165. Kibbe MR, et al. Iliac vein compression in an asymptomatic
patient population. J Vasc Surg. 2004;39:937–943.
166. Wolpert LM, et al. Magnetic resonance venography in the
diagnosis and management of May-Thurner syndrome. Vasc
Endovascular Surg. 2002;36(1):51–57.
167. Chung JW, et al. Acute iliofemoral deep vein thrombosis:
evaluation of underlying anatomic abnormalities by spiral CT
venography. J Vasc Interv Radiol. 2004;15:249–256.
168. Moreland NC, et al. Decreased incidence of left common iliac
vein compression in patients with abdominal aortic aneurysms.
J Vasc Surg. 2006;44:595–600.
169. Murray A, Halliday M, Croft RJ. Popliteal artery entrapment
syndrome. Br J Surg. 1991;78:1414–1419.
Downloaded for Nadiah An-Nur (nadiahnnr3@gmail.com) at Universitas Muslim Indonesia from ClinicalKey.com by Elsevier on October 16, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
170. Liu PT, et al. Popliteal vascular entrapment syndrome caused by
a rare anomalous slip of the lateral head of the gastrocnemius
muscle. Skeletal Radiol. 2005;34:359–363.
171. Leconte D, et al. An uncommon syndrome: the trapped popliteal
vein. Apropos of a case. J Chir (Paris). 1986;123(5):358–361.
172. Scarborough J, et al. Stenosis of the popliteal vein caused by
an osteochondroma of the distal femur: a case report. Diagn
Imaging. 1979;48:167–170.
173. Gerkin TM, et al. Popliteal vein entrapment presenting as deep
venous thrombosis and chronic venous insufficiency. J Vasc Surg.
1993;18:760–766.
174. Nicolaides AN, et al. Myocardial infarction and deep-vein
thrombosis. Br Med J. 1971;1:432–434.
175. Lensing AW, et al. Detection of deep-vein thrombosis by real-time
B-mode ultrasonography. N Engl J Med. 1989;320:342–345.
176. Kotilainen M, et al. Leg vein thrombosis diagnosed by
125I-fibrinogen test after acute myocardial infarction. Ann Clin
Res. 1973;5:365–368.
177. Simmons AV, Sheppard MA, Cox AF. Deep venous thrombosis
after myocardial infarction. Predisposing factors. Br Heart J. 1973;
35(6):623–625.
178. Huisman MV, Buller HR, ten Cate JW. Utility of impedance
plethysmography in the diagnosis of recurrent deep-vein throm-
bosis. Arch Intern Med. 1988;148:681–683.
179. Killewich LA, et al. Regression of proximal deep venous throm-
bosis is associated with fibrinolytic enhancement. J Vasc Surg.
1997;26:861–868.
180. van Ramshorst B, et al. Thrombus regression in deep venous
thrombosis. Quantification of spontaneous thrombolysis with
duplex scanning. Circulation. 1992;86:414–419.
181. Prandoni P, et al. A simple ultrasound approach for detec-
tion of recurrent proximal-vein thrombosis. Circulation.
1993;88:1730–1735.
182. Killewich LA, et al. Spontaneous lysis of deep venous thrombi:
rate and outcome. J Vasc Surg. 1989;9:89–97.
183. Heit JA, et al. Predictors of recurrence after deep vein thrombosis
and pulmonary embolism: a population-based cohort study.
Arch Intern Med. 2000;160(6):761–768.
184. Murin S, Romano PS, White RH. Comparison of outcomes
after hospitalization for deep venous thrombosis or pulmonary
embolism. Thromb Haemost. 2002;88(3):407–414.
185. Hull R, et al. Warfarin sodium versus low-dose heparin in
the long-term treatment of venous thrombosis. N Engl J Med.
1979;301:855–858.
186. Hull RD, et al. Continuous intravenous heparin compared
with intermittent subcutaneous heparin in the initial treat-
ment of proximal-vein thrombosis. N Engl J Med. 1986;315:
1109–1114.
187. Meissner MH, et al. Propagation, rethrombosis and new thrombus
formation after acute deep venous thrombosis. J Vasc Surg.
1995;22:558–567.
188. Lindblad B, Sternby NH, Bergqvist D. Incidence of venous
thromboembolism verified by necropsy over 30 years. BMJ. 1991;
302:709–711.